title: A neuronal correlate of secondary hyperalgesia in the rat spinal dorsal horn is submodality selective and facilitated by supraspinal influence.
abstract: Tissue injury produces hyperalgesia not only in the injured area (primary hyperalgesia) but also outside of it (secondary hyperalgesia). In the present investigation, the submodality selectivity and the contribution of supraspinal influence to a neural correlate of the secondary hyperalgesia induced by neurogenic inflammation was studied in the presumed pain relay neurons of the rat spinal dorsal horn. Mechanically and thermally evoked responses to wide-dynamic range (WDR) neurons of the spinal dorsal horn were recorded under sodium pentobarbital anesthesia in rats. Neurogenic inflammation was induced by application of mustard oil outside of the receptive fields of WDR neurons. To study the contribution of supraspinal influence to mustard oil-induced changes in neuronal responses, the spinal cord was transected at a midthoracic level or lidocaine was microinjected into the rostroventromedial medulla (RVM). Furthermore, the antidromically evoked compound volley in the sural nerve was determined to reveal excitability changes in the central terminals of primary afferent A-fibers induced by mustard oil. The results indicate that mustard oil adjacent to the receptive fields of spinal WDR neurons significantly enhanced their responses to mechanical but not to noxious heat stimuli, without a significant influence on their spontaneous activity. Both high- and low-threshold mechanoreceptive input to WDR neurons was equally facilitated, whereas mechanoreceptive input to spinal dorsal horn neurons mediating innocuous messages (low-threshold mechanoreceptive neurons) was not changed. Mustard oil in a remote site (forepaw) did not produce any hyperexcitability to responses evoked by hindpaw stimulation. Spinal transection or lidocaine block of the RVM significantly attenuated the mustard oil-induced mechanical hyperexcitability in spinal dorsal horn neurons. Mustard oil had no significant effect on a compound volley in the sural nerve induced by intraspinal stimulation of sural nerve terminals at a submaximal intensity. The selective mechanical hyperexcitability in spinal WDR neurons, without a change in their spontaneous activity, can be explained by a heterosynaptic facilitatory action on presynaptic terminals mediating mechanical signals to these nociceptive spinal neurons. These findings indicate that brain stem-spinal pathways, involving the RVM, do not only suppress nociception but under some pathophysiological conditions concurrent facilitatory influence may predominate and lead to enhancement of mechanical hyperexcitability. The descending facilitatory feed-back loop to nociceptive spinal neurons may help to protect the wounded tissue and thus promote healing.
authors.affiliation: Department of Physiology, University of Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Pertovaara
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D003714:Denervation; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D009149:Mustard Plant; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D009443:Neuritis / Q000139:chemically induced / Q000150:complications; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D010936:Plant Extracts / Q000494:pharmacology; D010938:Plant Oils; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D013118:Spinal Cord Diseases / Q000139:chemically induced / Q000150:complications; D013497:Sural Nerve / Q000503:physiopathology
chemical_list: D010936:Plant Extracts; D010938:Plant Oils; C027793:mustard oil